The purpose of this project is to study mechanisms of formation of supersaturated gallbladder bile and to develop methods to prevent supersaturation and gallstone formation. The follwoing findings were made this past year. The rates of recycling of cholic acid and chenodeoxycholic acid in the enterophepatic circulation was determined, and chenodeoxycholic acid was found to recirculate 1.34 times faster than cholic acid. This is probably due to more proximal absorption of chenodeoxycholic acid in the intestine. Despite these differences both bile acids were found to have the same effect on cholesterol absorption; specifically, chenodeoxycholic acid was not found to produce a reduction in cholesterol absorption as some other workers have reported. The effects of these two bile acids on hepatic secretion of biliary lipids were studied in more detail. Chenodeoxycholic acid was found to reduce bile saturation with cholesterol more than cholic acid, and these differences appeared to be due either to differential effects on biliary lipid interrelationships at the site of their secretion and/or differential inhibition of cholesterol synthesis by the liver. Two other studies were carried out during this past year. In one, we observed that patients with moderately advanced, compensated cirrhosis do not have a marked disturbance of metabolism of cholesterol and bile acids as has been noted in patients with advanced, decompensated cirrhosis; however, mild changes in biliary lipid metabolism anticipate those found in more severe cirrhosis. Finally, we studied sucrose polyester which is a nonabsorbable, fat-like material that has been shown to lower plasma cholesterol in man. In our study, we found a significant lowering of plasma cholesterol, and the percent saturation of gallbladder bile was not affected adversely.